fluorouracil plus ucn-01 in treating patients with advanced or refractory solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. ucn-01 may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug. purpose: phase i trial to study the effectiveness of fluorouracil plus ucn-01 in treating patients who have advanced or refractory solid tumors.

objectives: * determine the maximum tolerated dose, dose limiting toxicity, and toxicity profile of fluorouracil with ucn-01 in patients with advanced or refractory solid tumors. * assess the clinical pharmacokinetics of this regimen and correlate with observed toxicities in these patients. * obtain preliminary data on the therapeutic activity of this regimen in these patients. outline: this is a dose escalation study of fluorouracil. patients receive fluorouracil iv over 24 hours on days 1, 8, 15, and 22. patients receive an initial dose of ucn-01 iv over 72 hours beginning on day 2 during course 1 and then maintenance ucn-01 iv over 36 hours beginning on day 2 during subsequent courses. treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of fluorouracil until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. projected accrual: approximately 6-48 patients will be accrued for this study within approximately 14 months.

Eligibility criteria:
disease characteristics: * histologically confirmed solid tumor that is refractory to standard therapy or for which no standard therapy exists * measurable or evaluable disease * no cns metastasis or primary cns malignancy patient characteristics: age: * 18 and over performance status: * karnofsky 60-100% life expectancy: * not specified hematopoietic: * wbc greater than 3,500/mm\^3 * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 1.5 mg/dl * sgot and sgpt no greater than 2.5 times upper limit of normal renal: * creatinine no greater than 1.5 mg/dl or * creatinine clearance greater than 60 ml/min cardiovascular: * no history of coronary artery disease documented by prior myocardial infarction, angiography, or coronary-artery bypass grafting * no cardiac arrhythmias or congestive heart failure within the past 6 months * stable atrial fibrillation on standard treatment allowed at discretion of investigator pulmonary: * dlco at least 60% of predicted other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 2 months after study * no active serious or uncontrolled infection * hiv negative * no diabetes * no other medical condition that would preclude study prior concurrent therapy: * see disease characteristics biologic therapy: * at least 4 weeks since prior immunotherapy and recovered chemotherapy: * at least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered * prior fluorouracil allowed endocrine therapy: * not specified radiotherapy: * no prior mediastinal radiotherapy * at least 4 weeks since prior radiotherapy and recovered surgery: * not specified other: * no concurrent anticonvulsant medications

Keywords: unspecified adult solid tumor, protocol specific